OBJECTIVE: To determine the efficacy of succimer chelation therapy in alleviating lead toxicity in monkeys and to determine the endogenous sources of lead remobilized. This study evaluates neurobehavioral and physiological endpoints and parallels clinical trials in children. RESULTS We began analyzing vast amounts of behavioral and physiological data collected in 1997 There is a need to validate the efficacy of chelation agents such as succimer not only to reduce body lead stores in children but to alleviate neurobehavioral and target organ toxicity. Treatment groups of monkeys are divided into no lead exposure (controls), one year of daily lead intake, and two years of daily lead intake. Lead administration begins at birth. We maintain monkeys receiving lead at a target blood lead concentrations of 35 g Pb/d during lead intake, which falls near the midrange of the planned clinical trials of succimer. Monkeys receive two treatment regimes of succimer beginning at approximately 12 and 15 months of age. The groups given lead until two years of age parallel cases in which children return to lead contaminated environments following chelation therapy. We monitor the efficacy of succimer in reversing neurobehavioral deficits with a broad range of behavioral tests administered over the course of the three therapies and after completion of all chelations, the latter to evaluate the long term efficacy of succimer therapy on neurobehavioral processes. We use lead-induced alterations in the heme biosynthetic pathway as sensitive biomarkers of systemic organ lead toxicity. An established stable-lead isotope technique determines the removal of lead from skeletal and soft tissue stores. K-X-ray fluorescence techniques assess long-term changes in reduction of skeletal lead due to chelation in adolescent monkeys. Results should provide valuable data on the efficacy of succimer to alleviate neurobehavioral and target organ toxicity in children. FUTURE DIRECTIONS To continue collecting and analyzing all behavioral and physiological data. KEY WORDS lead, monkeys, chelation, succimer, learning, social behavior, activity, stable isotopes